We propose to characterize the MLR (HLA-D) locus alleles in approximately 300 patients with Hodgkin's disease or cancer of the breast, lungs, cervix, colon and prostate, and to compare the frequency of these alleles to a normal population of approximately 100 persons who will be studied in the same way. The HLA genetic locus is located on chromosome 6 in man and is part of the Major Histocompatibility Complex. In mice, genes in the analogous H2 complex are strongly associated with susceptibility to virally-induced leukemia and other forms of cancer. In man, dogs and Rhesus monkeys the MLR locus is located at one end of this major histocompatibility complex, at a site rather distant from the serologically defined HLA loci, A-, B-, and C-. It is in this region that the Ir genes controlling immune responsiveness to synthetic polymeric antigens have been placed in studies of Rhesus monkeys. It would appear then that unless entire haplotypes of this genetic region are involved in the genetics of cancer, studying the HLA-D locus would be the most appropriate area to seek a "cancer susceptibility" gene(s). Until recently, however, HLA-D locus typing has been logistically impractical because of the need for fresh blood from a large humber of HLA-D homozygous donors for mixed leukocyte cultures. We have established longterm lymphoblastoid cell lines on over 50 HLA-D homozygous typing donors from many different parts of the world: these lines can be used for HLA-D typing in place of fresh blood from each typing donor. The information gained by the proposed studies could have far-reaching effects in identifying "high-cancer risk" genes, haplotypes, patients and families, and should also serve to enhance our understanding of the genetics of histocompatibility matching for organ transplantation. During the first year, we typed a normal population of 100 persons and compared the results of our method of HLA-D typing with those of conventional HLA-D typing. There was over 85% agreement between the two methods. In addition, we have further refined the technique by computer analysis and by using smaller amounts of blood since we anticipate using an enlarged cell panel in subsequent studies of cancer patients. These studies now require less than 8ml of blood from each patient.